Life and death

by A. Dastre

This analysis of albuminous matter at first requires great precautions. The chemist finds himself in the presence of architecture of a very subtle kind. The molecule of albumin is a complex edifice which has used up several thousand atoms. To perceive the plan and structure, it must be dismantled and separated into parts which are neither too large nor too small. Such careful demolition is difficult. Processes too rough or too violent will reduce the whole to the tiniest of fragments. It is a statue which may be reduced to dust, instead of being separated into recognizable fragments, easily fitted in place along their fractured faces.

Analysis of Albumin by Schützenberger.—Schützenberger, a chemist of great merit, attempted (about 1875) this thankless task. Others before him had experimented in various ways. Two Austrian scientists, Hlasitwetz and Habermann, in 1873, and a little later Drechsel in 1892, had used concentrated hydrochloric acid to break down albumin. They also employed bromine for the same purpose. More recently Fuerth had used nitric acid with a similar object. Schützenberger tried another way. The battering ram which he used against the edifice of albumin was a concentrated alkali, baryta. He warmed the white of an egg with barium hydrate in a closed vessel at a temperature of 200°. The albumin of egg then divides into a certain number of simpler groups. The difficulty is to isolate and to recognize each part in this mass of the materials of demolition. That can be done by the aid of the processes of direct analysis. By mentally combining these different fragments, the original building is reconstructed. This method of demolition is certainly too rough and violent. Schützenberger’s operation gives us very fine fragments—small molecules of free hydrogen, of ammonia, of carbonic, acetic, and oxalic, acids which reveal extreme pulverization. These products represent about a quarter of the total mass. The other three-quarters are formed of larger fragments, the examination of which is most instructive. They belong to four groups. The first comprises five or six bodies, amido-acids or leucins. It proves the existence in the molecule of albumin of compounds of the series of fats—i.e., arranged in an open chain. The second group is formed by tyrosin and kindred products—i.e., by the bodies of the aromatic series, which force us to acknowledge the presence in the molecule of albumin of a benzene nucleus. The third group forms around the nucleus known to chemists under the name of pyrrol. The fourth comprises bodies such as the glucoproteins, connected with the sugars, or carbohydrates.

Does the fact that the molecule of albumin is destroyed in producing these compounds raise the question as to whether it implies the idea that in reality they pre-exist in it? Chemists are rather inclined to admit this. However, the conclusion does not appear to be permissible. Duclaux considers it doubtful. It is not certain that all these fragmentary bodies pre-exist in reality, and it is no more certain that a simple bringing of them together represents the primitive edifice. Materials of demolition from a house that has been pulled down give no idea of its natural architectural character. There is only one way of justifying the hypothesis, and that is to reconstitute the original molecule of albumin by bringing the fragments together. We have not got to that stage yet. The era of syntheses of such complexity is more or less near, but it has certainly not yet begun.

Moreover, it is not correct to say that the simple juxtaposition of the surfaces of fracture will reproduce the initial body. The fragments, so far as analysis has obtained them, are not absolutely what they might have been in the original structure. There they adhered the one to the other, not only by the mere contact of their surfaces of fracture, as is supposed, but in a slightly more complex manner. The fragments of the molecule are joined by bonds. We can picture them to ourselves by supposing these bonds to be like hooks. The hooks, which could only be broken by violence, are called by the chemists satisfied atomicities. These atomicities, set free by the breaking up, cannot remain in this condition; they must be satisfied anew. The hook tries to attach itself. In Schützenberger’s experiment the addition of water provides for this necessity. A molecule of water (H₂O) splits into two, the hydrogen (H) on the one side and the hydroxyl (OH) on the other. These two elements cling to the liberated bonds of the fragments of the molecule of albumin, and thus the bodies were found complete. Schützenberger’s experiment was too violent, too radical, and it gave too large a number of fragments, with their free hooks and atomicities unsatisfied, for rather a large proportion of the water added disappeared during the experiment. In one case this quantity was as much as 17 grammes per 100 grammes of albumin. The molecules of this water were employed in the reparation of the incomplete fragmentary molecules of the albumin.

It follows that Schützenberger’s experiment gave too large a number of very small pieces corresponding to far too great a pulverization. The very small fragments are the molecules of acids such as acetic acid, oxalic acid, carbonic acid, molecules of ammonia, and even of hydrogen, which we know we are setting free.

But, apart from these products which represent a quarter of the molecule of albumin submitted to analysis, the other three quarters represent larger fragments which may be considered as the real constituents of the building. Thus we find four kinds of groups which may be accepted as natural. The first of these groups is that of the leucins or amido-acids. It proves the existence in the molecule of albumin of compounds of the fatty series. There is also an aromatic group—a pyridine group—and a group belonging to the category of sugars. Imagine a certain grouping of these four series. This would be the nucleus of the molecule of albumin. If we graft on to this nucleus, on to this framework as it were, so many annexes, or lateral chains, the building will be loaded with embellishments; it will have been made unstable and ipso facto appropriate for the part that it plays in the incessant transformations of the organism.

Kossel’s Analysis. Hexonic Nucleus.—Kossel has approached the problem in another fashion. He did not attempt to attack the albumin of the egg. This body is, in fact, a heterogeneous mixture as complex as the needs of the embryo of which it forms the food. Kossel tried a physiologically simpler albuminoid. He got it from an anatomical element having no nutritive rôle, of a very elementary organization and physiological functional activity, and yet one of energetic vitality—the male generating cell. Instead of the hen’s egg he therefore analyzed the milt of fish, and, in the first place, of salmon. As was to be expected from what has been said of the proteids, this living matter gives a combination of the nuclein, already known, with an albumin. The latter is abundant, forming a quarter of the total mass. Its reaction is strongly alkaline, which is the general characteristic of the variety of albumin known by the name of histones. Miescher, the learned chemist of Basle, who had noticed this basic albumin when working on the Rhine salmon, gave it the name of protamin. This is the substance submitted by Kossel to analysis in preference to the albumin of egg, so dear to the chemists who had preceded him. The disintegration of this molecule, instead of giving the series of bodies obtained by Schützenberger, gave but one, a real chemical base, arginin. At the first trial the albumin examined was reduced to a simple crystallizable element. The conclusion was obvious. The protamin of salmon is the simplest of albumins. To form this elementary proteid substance a hexonic base with water is all that is required.

Continuing on these lines other male generating cells were examined and a series of protamines constructed on the same type was found, and these albuminous bodies proved to be formed of a base or mixture of analogous hexonic bases: arginin, histidin, and lysin—all bodies closely akin in their properties and entirely belonging to the physical world.

Once aware of the existence of this fundamental nucleus, chemists found it in the more complex albumins where it had been missed. It was found in the albumin of egg hidden under the mass of other groups. It was recognized in all animal or vegetable albumins. The nuclei of Schützenberger may be missing. Hexonic bases are the constant and universal element of all varieties of albumins. They prevail in the chemical nucleus of the albuminous molecule, and perhaps as is suggested by Kossel, they may form it exclusively. All the other elements are superadded and accessory. The essential type of this molecular edifice, sought for so long, is known at last.

Conclusion.—To sum up, the chemical unity of living beings is expressed by saying that living matter, protoplasm, is a mixture or a complex of proteid substances with an hexonic nucleus.